The bipolar disorders are mood disorders in which a disturbance in mood is the predominant feature. Bipolar I disorder is characterized by one or more manic or mixed episodes, usually accompanied by major depressive episodes. Bipolar II disorder is distinguished by primarily major depressive episodes accompanied by at least spontaneous hypomanic episodes according to Diagnostics and Statistical Manual of Mental Disorders, Edition—IV, American Psychiatric Association, Washington D.C. (DSM-IV). Bipolar depression refers to the major depressive episodes that occur along the course of bipolar I and II disorder.
In the U.S., the prevalence of bipolar disorder is estimated to be 1 to 3.5%, evenly divided between men and women. The length of time between onset and symptoms with proper diagnosis and treatment is approximately 10 years. It is estimated that only 60% of those suffering from a bipolar disorder are receiving appropriate pharmacotherapy.
Although there is extensive and emerging literature guiding the treatment of the manic phase of bipolar I disorder as well as many approved compounds for the treatment of unipolar depression, the treatment of bipolar depression has not been widely studied and treatment guidelines are in their infancy. The use of currently available antidepressants for monotherapy for bipolar depression is often problematic as they may increase the “switch” into hypomania or mania from depression, or increase cycle acceleration. Further, patients can experience treatment-emergent mania with antidepressant monotherapy. The long term use of mood stabilizing medications such as lithium carbonate (Li2CO3) is common and may decrease the likelihood of these complications.
Amisulpride is a recent atypical antipsychotic with a pharmacological and clinical profile that differs from that of other atypical agents. Amisulpride (Solian®, Lorex, Sanofi-aventis), a benzamide derivative, is closely related to sulpiride, licensed for the treatment of schizophrenia and negative symptoms associated with schizophrenia. Amisulpride is a selective dopamine D2/D3 antagonist (J Pharmacol Exp Ther 1997, 280/1:83-97) and has been the most thoroughly evaluated atypical antipsychotic for the treatment of negative symptoms (Br J Psychiatry 1999, 170: 18-22; Am J Psychiatry 1999, 156/4: 610-616). Amisulpride recommended daily doses are 400-800 mg (maximum 1200 mg) for acute psychotic episodes, and 50-300 mg for patients with predominantly negative symptoms.
The synthesis of amisulpride is described in U.S. Pat. No. 4,401,822.
A literature search demonstrates that, as in the case with many other antipsychotic drugs, there has been a wide use of amisulpride as an add-on in many psychiatric disorders. In a few papers amisulpride has been used among other drugs as add-on to treatment for bipolar disorders.
Recently, the relapse rate in an open label follow-up study on amisulpride in the add-on treatment of bipolar I patients has been measured. Clinical Practice and Epidemiology in Mental Health 2006, 2:19. A statistically significant decrease in overall relapse rate was observed during the period of amisulpride therapy, but only manic episodes reached statistical significance.